HSV-1 promotes Ca 2+-mediated APP phosphorylation and Aβ accumulation in rat cortical neurons

Roberto Piacentini, Livia Civitelli, Cristian Ripoli, Maria Elena Marcocci, Giovanna De Chiara, Enrico Garaci, Gian Battista Azzena, Anna Teresa Palamara, Claudio Grassi

Research output: Contribution to journalArticle

Abstract

Epidemiological and experimental findings suggest that chronic infection with Herpes simplex virus type 1 (HSV-1) may be a risk factor for Alzheimer's disease (AD), but the molecular mechanisms underlying this association have not been fully identified. We investigated the effects of HSV-1 on excitability and intracellular calcium signaling in rat cortical neurons and the impact of these effects on amyloid precursor protein (APP) processing and the production of amyloid-β peptide (Aβ). Membrane depolarization triggering firing rate increases was observed shortly after neurons were challenged with HSV-1 and was still evident 12 hours postinfection. These effects depended on persistent sodium current activation and potassium current inhibition. The virally induced hyperexcitability triggered intracellular Ca 2+ signals that significantly increased intraneuronal Ca 2+ levels. It also enhanced activity- and Ca 2+-dependent APP phosphorylation and intracellular accumulation of Aβ42. These findings indicate that HSV-1 causes functional changes in cortical neurons that promote APP processing and Aβ production, and they are compatible with the co-factorial role for HSV-1 in the pathogenesis of AD suggested by previous findings.

Original languageEnglish
JournalNeurobiology of Aging
Volume32
Issue number12
DOIs
Publication statusPublished - Dec 2011

Keywords

  • Alzheimer's disease
  • Amyloid precursor protein
  • Amyloid-β peptide
  • APP phosphorylation
  • Ca 1 channels
  • Herpes simplex virus type 1
  • Intracellular Ca signals
  • Persistent Na currents

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology

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